The long-term objective of this research is to understand the pathobiology of the skin blistering disorders known as epidermolysis bullosa simplex (EBS). Weber-Cockayne is one of at least five clinical subtypes of EBS, all characterized by autosomal dominant inheritance and nonscarring intraepidermal blisters induced by seemingly mild trauma. The specific aims of the project are: 1) to identify, collect, and construct a repository of immortalized cell lines of patients and families affected with the Weber-Cockayne subtype (EBS-WC), 2) to test candidate genes and to use mapped DNA markers to search the genome for linkage to the EBS-WC gene, 3) to confirm the linkage, and 4) to identify, collect and construct immortalized cell lines of families/individuals affected with other subtypes of EBS, in particular Koebner and DowlingMeara, to test if they are allelic to EBS-WC. The power of our approach is that it requires no a priori knowledge or assumptions concerning the EBS-WC gene location, structure, or function. Power calculations show that the 13 EBS-WC families we have identified for this study have substantial power to detect linkage. We have >85% power of obtaining significant evidence in favor of linkage at a recombination fraction of 10% even with only modestly informative markers (PIC=0.3). Analyses under conditions of closer linkage ana/or more informative markers indicate power of 90-99% of exceeding a LOD score of 3 with a linked marker. Mapping the EBS-WC gene could eventually lead to an understanding of the molecular basis for EB simplex disease and the genetic and biochemical relationships between the different clinical subtypes of EBS.